Scholars@Duke
Ayako Suzuki

Ayako Suzuki

Associate Professor of Medicine
Medicine, Gastroenterology
ayako.suzuki@duke.edu
Duke Box 3913, Durham, NC 27710
Duke South Orange Zone, Room 0, Duke University Medical Center, Durham, NC 27710
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Selected Publications

Antimullerian Hormone, a Marker of Ovarian Reserve, Is Protective Against Presence and Severity of NASH in Premenopausal Women.

Journal Article Clin Gastroenterol Hepatol · February 2024 BACKGROUND & AIMS: Antimüllerian hormone (AMH) is a marker of ovarian reserve with emerging data linking lower levels to some metabolic and inflammatory diseases in women. Whether AMH levels influence nonalcoholic fatty liver disease (NAFLD) is unknown. ME ... Full text Link to item Cite

Lower hepatic CBS and PEMT expression in advanced NAFLD: inferencing strategies to lower homocysteine with a mathematical model

Journal Article Metabolism and Target Organ Damage · January 1, 2024 Aim: Hepatic homocysteine (Hcy) accumulation promotes inflammation and fibrosis in experimental nonalcoholic fatty liver disease (NAFLD), while vitamin B12 and folate reduce hepatic Hcy and protect animals from nonalcoholic steatohepatitis. This suggests c ... Full text Cite

Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression.

Journal Article Hepatology · October 1, 2023 BACKGROUND AND AIMS: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes a ... Full text Link to item Cite

A phase 2, adaptive randomized, double-blind, placebo-controlled, multicenter, 52-week study of HM15211 in patients with biopsy-confirmed non-alcoholic steatohepatitis - Study design and rationale of HM-TRIA-201 study.

Journal Article Contemp Clin Trials · July 2023 Non-alcoholic steatohepatitis (NASH) is a multifactorial disease with an increasing prevalence worldwide due to the obesity pandemic. HM15211 (efocipegtrutide), a novel, long-acting glucagon-like peptide-1/glucagon/glucose-dependent insulinotropic polypept ... Full text Link to item Cite

Statistical methods for exploring spontaneous adverse event reporting databases for drug-host factor interactions.

Journal Article BMC Med Res Methodol · March 27, 2023 BACKGROUND: Drug toxicity does not affect patients equally; the toxicity may only exert in patients who possess certain attributes of susceptibility to specific drug properties (i.e., drug-host interaction). This concept is crucial for personalized drug sa ... Full text Link to item Cite

Assessment of the Frequency, Phenotypes, and Outcomes of Acute Liver Injury Associated with Amoxicillin/Clavulanate in 1.4 Million Patients in the Veterans Health Administration.

Journal Article Drug Saf · February 2023 INTRODUCTION: Drug-induced liver injury is a significant health issue, yet the exposure-based incidence remains to be characterized. OBJECTIVE: We aimed to assess the frequency, phenotypes, and outcomes of acute liver injury associated with amoxicillin/cla ... Full text Link to item Cite

Concise review: Breastfeeding, lactation, and NAFLD. An updated view of cross-generational disease transmission and prevention

Journal Article Metabolism and Target Organ Damage · January 1, 2023 Evidence suggests that breastfeeding protects the mother-infant dyad against the development and progression of nonalcoholic fatty liver disease (NAFLD). In this context, we aim to provide insight into the most notable and representative epidemiological st ... Full text Cite

Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans.

Journal Article J Gen Intern Med · December 2022 BACKGROUND: Many severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive patients take commonly prescribed medications with properties which may affect mortality. OBJECTIVE: Assess if common medications postulated to affect clinical outcomes ... Full text Link to item Cite

A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality.

Journal Article Am J Respir Crit Care Med · November 15, 2022 Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35 ... Full text Link to item Cite

Vitamin B12 and folate decrease inflammation and fibrosis in NASH by preventing syntaxin 17 homocysteinylation.

Journal Article J Hepatol · November 2022 BACKGROUND & AIMS: Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B12 (B12) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it ... Full text Link to item Cite

Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression.

Journal Article Nat Commun · September 3, 2022 Spermidine is a natural polyamine that has health benefits and extends life span in several species. Deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) are key enzymes that utilize spermidine to catalyze the post-translational hypusination ... Full text Link to item Cite

Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID-19.

Journal Article Clin Transl Sci · August 2022 Remdesivir is the first US Food and Drug Administration (FDA)-approved drug for the treatment of coronavirus disease 2019 (COVID-19). We conducted a retrospective pharmacogenetic study to examine remdesivir-associated liver enzyme elevation among Million V ... Full text Link to item Cite

Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.

Journal Article JAMA Intern Med · August 1, 2022 IMPORTANCE: Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the ass ... Full text Link to item Cite

APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program.

Journal Article JAMA Intern Med · April 1, 2022 IMPORTANCE: Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates. OBJECTIVE: Individuals with African ancestry with 2 copies of apolipoprotein L1 (APOL1) varian ... Full text Link to item Cite

Antimullerian Hormone, a Marker of Ovarian Reserve, Is Protective Against Presence and Severity of NASH in Premenopausal Women.

Journal Article Clin Gastroenterol Hepatol · February 2024 BACKGROUND & AIMS: Antimüllerian hormone (AMH) is a marker of ovarian reserve with emerging data linking lower levels to some metabolic and inflammatory diseases in women. Whether AMH levels influence nonalcoholic fatty liver disease (NAFLD) is unknown. ME ... Full text Link to item Cite

Lower hepatic CBS and PEMT expression in advanced NAFLD: inferencing strategies to lower homocysteine with a mathematical model

Journal Article Metabolism and Target Organ Damage · January 1, 2024 Aim: Hepatic homocysteine (Hcy) accumulation promotes inflammation and fibrosis in experimental nonalcoholic fatty liver disease (NAFLD), while vitamin B12 and folate reduce hepatic Hcy and protect animals from nonalcoholic steatohepatitis. This suggests c ... Full text Cite

Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression.

Journal Article Hepatology · October 1, 2023 BACKGROUND AND AIMS: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes a ... Full text Link to item Cite

A phase 2, adaptive randomized, double-blind, placebo-controlled, multicenter, 52-week study of HM15211 in patients with biopsy-confirmed non-alcoholic steatohepatitis - Study design and rationale of HM-TRIA-201 study.

Journal Article Contemp Clin Trials · July 2023 Non-alcoholic steatohepatitis (NASH) is a multifactorial disease with an increasing prevalence worldwide due to the obesity pandemic. HM15211 (efocipegtrutide), a novel, long-acting glucagon-like peptide-1/glucagon/glucose-dependent insulinotropic polypept ... Full text Link to item Cite

Statistical methods for exploring spontaneous adverse event reporting databases for drug-host factor interactions.

Journal Article BMC Med Res Methodol · March 27, 2023 BACKGROUND: Drug toxicity does not affect patients equally; the toxicity may only exert in patients who possess certain attributes of susceptibility to specific drug properties (i.e., drug-host interaction). This concept is crucial for personalized drug sa ... Full text Link to item Cite

Assessment of the Frequency, Phenotypes, and Outcomes of Acute Liver Injury Associated with Amoxicillin/Clavulanate in 1.4 Million Patients in the Veterans Health Administration.

Journal Article Drug Saf · February 2023 INTRODUCTION: Drug-induced liver injury is a significant health issue, yet the exposure-based incidence remains to be characterized. OBJECTIVE: We aimed to assess the frequency, phenotypes, and outcomes of acute liver injury associated with amoxicillin/cla ... Full text Link to item Cite

Concise review: Breastfeeding, lactation, and NAFLD. An updated view of cross-generational disease transmission and prevention

Journal Article Metabolism and Target Organ Damage · January 1, 2023 Evidence suggests that breastfeeding protects the mother-infant dyad against the development and progression of nonalcoholic fatty liver disease (NAFLD). In this context, we aim to provide insight into the most notable and representative epidemiological st ... Full text Cite

Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans.

Journal Article J Gen Intern Med · December 2022 BACKGROUND: Many severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive patients take commonly prescribed medications with properties which may affect mortality. OBJECTIVE: Assess if common medications postulated to affect clinical outcomes ... Full text Link to item Cite

A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality.

Journal Article Am J Respir Crit Care Med · November 15, 2022 Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35 ... Full text Link to item Cite

Vitamin B12 and folate decrease inflammation and fibrosis in NASH by preventing syntaxin 17 homocysteinylation.

Journal Article J Hepatol · November 2022 BACKGROUND & AIMS: Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B12 (B12) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it ... Full text Link to item Cite

Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression.

Journal Article Nat Commun · September 3, 2022 Spermidine is a natural polyamine that has health benefits and extends life span in several species. Deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) are key enzymes that utilize spermidine to catalyze the post-translational hypusination ... Full text Link to item Cite

Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID-19.

Journal Article Clin Transl Sci · August 2022 Remdesivir is the first US Food and Drug Administration (FDA)-approved drug for the treatment of coronavirus disease 2019 (COVID-19). We conducted a retrospective pharmacogenetic study to examine remdesivir-associated liver enzyme elevation among Million V ... Full text Link to item Cite

Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.

Journal Article JAMA Intern Med · August 1, 2022 IMPORTANCE: Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the ass ... Full text Link to item Cite

APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program.

Journal Article JAMA Intern Med · April 1, 2022 IMPORTANCE: Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates. OBJECTIVE: Individuals with African ancestry with 2 copies of apolipoprotein L1 (APOL1) varian ... Full text Link to item Cite

A novel phenotype-based drug-induced liver injury causality assessment tool (DILI-CAT) allows for signal confirmation in early drug development.

Journal Article Aliment Pharmacol Ther · April 2022 BACKGROUND: Drug-induced liver injury (DILI) requires accurate case adjudication, with expert opinion being the current best practice. AIM: We utilised a novel DILI causality assessment tool (DILI-CAT), which uses drug-specific liver injury phenotypes, to ... Full text Link to item Cite

Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis.

Journal Article Nat Commun · January 31, 2022 Nonalcoholic fatty liver disease (NAFLD) is an important health concern worldwide and progresses into nonalcoholic steatohepatitis (NASH). Although prevalence and severity of NAFLD/NASH are higher in men than premenopausal women, it remains unclear how sex ... Full text Link to item Cite

Interaction of Vitamin D and Corticosteroid Use in Hospitalized COVID-19 Patients: A Potential Explanation for Inconsistent Findings in the Literature.

Journal Article Curr Pharm Des · 2022 Vitamin D is an important immune-modulator with anti-inflammatory properties. While this prohormone has been studied extensively in the prevention and treatment of COVID-19, findings have been inconsistent regarding its overall benefit in patients hospital ... Full text Link to item Cite

Associations Between Gastrointestinal Symptoms and COVID-19 Severity Outcomes Based on a Propensity Score-Weighted Analysis of a Nationwide Cohort.

Journal Article Gastro Hep Adv · 2022 BACKGROUND AND AIMS: Gastrointestinal (GI) symptoms are well-recognized manifestations of coronavirus disease 2019 (COVID-19). Our primary objective was to evaluate the association between GI symptoms and COVID-19 severity. METHODS: In this nationwide coho ... Full text Link to item Cite

A novel quantitative computer-assisted drug-induced liver injury causality assessment tool (DILI-CAT).

Journal Article PLoS One · 2022 BACKGROUND AND AIMS: We hypothesized that a drug's clinical signature (or phenotype) of liver injury can be assessed and used to quantitatively develop a computer-assisted DILI causality assessment-tool (DILI-CAT). Therefore, we evaluated drug-specific DIL ... Full text Link to item Cite

The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2.

Journal Article Int J Environ Res Public Health · December 31, 2021 This data-based cohort consisted of 26,508 (7%) United States veterans out of the 399,290 who tested positive for SARS-CoV-2 from 1 March to 10 September 2020. We aimed to assess the interaction of post-index vitamin D (Vit D) and corticosteroid (CRT) use ... Full text Link to item Cite

Hepatic Mitochondrial SAB Deletion or Knockdown Alleviates Diet-Induced Metabolic Syndrome, Steatohepatitis, and Hepatic Fibrosis.

Journal Article Hepatology · December 2021 BACKGROUND AND AIMS: The hepatic mitogen-activated protein kinase (MAPK) cascade leading to c-Jun N-terminal kinase (JNK) activation has been implicated in the pathogenesis of nonalcoholic fatty liver (NAFL)/NASH. In acute hepatotoxicity, we previously ide ... Full text Link to item Cite

COVID-19-Associated Mortality in US Veterans with and without SARS-CoV-2 Infection.

Journal Article Int J Environ Res Public Health · August 11, 2021 BACKGROUND: We performed an observational Veterans Health Administration cohort analysis to assess how risk factors affect 30-day mortality in SARS-CoV-2-infected subjects relative to those uninfected. While the risk factors for coronavirus disease 2019 (C ... Full text Open Access Link to item Cite

Elevated bilirubin, alkaline phosphatase at onset, and drug metabolism are associated with prolonged recovery from DILI.

Journal Article J Hepatol · August 2021 BACKGROUND & AIMS: Although most drug-induced liver injury (DILI) cases resolve after the offending medication is discontinued, time to recovery varies among patients, with 6 -12% developing a chronic disease. Herein, we investigated clinical factors and d ... Full text Link to item Cite

Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD.

Journal Article Clin Gastroenterol Hepatol · June 2021 BACKGROUND & AIMS: Higher testosterone contributes to imaging-confirmed nonalcoholic fatty liver disease (NAFLD) in women, but whether testosterone influences their disease severity is unknown. METHODS: The association of free testosterone (free T) with no ... Full text Link to item Cite

Drug properties and host factors contribute to biochemical presentation of drug-induced liver injury: a prediction model from a machine learning approach.

Journal Article Arch Toxicol · May 2021 Drug-induced liver injury (DILI) presentation varies biochemically and histologically. Certain drugs present quite consistent injury patterns, i.e., DILI signatures. In contrast, others are manifested as broader types of liver injury. The variety of DILI p ... Full text Link to item Cite

REPLY.

Journal Article Hepatology · April 2021 Full text Link to item Cite

Sex and Menopause Modify the Effect of Single Nucleotide Polymorphism Genotypes on Fibrosis in NAFLD.

Journal Article Hepatol Commun · April 2021 The development of fibrosis in nonalcoholic fatty liver disease (NAFLD) is influenced by genetics, sex, and menopausal status, but whether genetic susceptibility to fibrosis is influenced by sex and reproductive status is unclear. Our aim was to identify m ... Full text Link to item Cite

Low Testosterone Is Associated With Nonalcoholic Steatohepatitis and Fibrosis Severity in Men.

Journal Article Clin Gastroenterol Hepatol · February 2021 With rising prevalence of obesity and diabetes, nonalcoholic fatty liver disease (NAFLD) is now a leading cause of chronic liver disease. One-third of obese or diabetic men have subnormal free and bioavailable testosterone concentrations.1 Several studies ... Full text Link to item Cite

Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study.

Journal Article BMC Cancer · January 25, 2021 BACKGROUND: There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. METHODS: We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to S ... Full text Link to item Cite

Sex Hormone Relations to Histologic Severity of Pediatric Nonalcoholic Fatty Liver Disease.

Journal Article J Clin Endocrinol Metab · November 1, 2020 CONTEXT: Sex hormones have been linked with presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults, but it is unknown if they affect severity of pediatric NAFLD. OBJECTIVE: To examine associations of circulating SHBG, estrogens, and an ... Full text Link to item Cite

Sex and gender: modifiers of health, disease, and medicine.

Journal Article Lancet · August 22, 2020 Clinicians can encounter sex and gender disparities in diagnostic and therapeutic responses. These disparities are noted in epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment. This Review discusses the fu ... Full text Link to item Cite

Sexual Dimorphism of NAFLD in Adults. Focus on Clinical Aspects and Implications for Practice and Translational Research.

Journal Article J Clin Med · April 28, 2020 Nonalcoholic fatty liver disease (NAFLD) embraces the clinico-pathological consequences of hepatic lipotoxicity and is a major public health problem globally. Sexual dimorphism is a definite feature of most human diseases but, under this aspect, NAFLD lags ... Full text Link to item Cite

Increased Glutaminolysis Marks Active Scarring in Nonalcoholic Steatohepatitis Progression.

Journal Article Cell Mol Gastroenterol Hepatol · 2020 BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) occurs in the context of aberrant metabolism. Glutaminolysis is required for metabolic reprograming of hepatic stellate cells (HSCs) and liver fibrogenesis in mice. However, it is unclear how changes i ... Full text Open Access Link to item Cite

Sex disparity in hepatocellular carcinoma owing to NAFLD and non-NAFLD etiology: epidemiological findings and pathobiological mechanisms

Journal Article Hepatoma Research · January 1, 2020 Nonalcoholic fatty liver disease (NAFLD) exhibits sexual dimorphism, with men being more exposed than women to the risk of simple steatosis, nonalcoholic steatohepatitis fibrosis, and hepatocellular carcinoma (HCC), while the protection conferred to women ... Full text Cite

Expression of mitochondrial membrane-linked SAB determines severity of sex-dependent acute liver injury.

Journal Article J Clin Invest · December 2, 2019 SH3 domain-binding protein that preferentially associates with Btk (SAB) is an outer-membrane docking protein for JNK-mediated impairment of mitochondrial function. Deletion of Sab in hepatocytes inhibits sustained JNK activation and cell death. The curren ... Full text Link to item Cite

Sex Differences in Nonalcoholic Fatty Liver Disease: State of the Art and Identification of Research Gaps.

Journal Article Hepatology · October 2019 Despite tremendous research advancements in nonalcoholic fatty liver disease (NAFLD), our understanding of sex differences in NAFLD remains insufficient. This review summarizes the current knowledge on sex differences in NAFLD, identifies gaps, and discuss ... Full text Link to item Cite

Drug-induced liver injury.

Journal Article Nat Rev Dis Primers · August 22, 2019 Drug-induced liver injury (DILI) is an adverse reaction to drugs or other xenobiotics that occurs either as a predictable event when an individual is exposed to toxic doses of some compounds or as an unpredictable event with many drugs in common use. Drugs ... Full text Link to item Cite

Tools for causality assessment in drug-induced liver disease.

Journal Article Curr Opin Gastroenterol · May 2019 PURPOSE OF REVIEW: There are three liver-specific causality assessment tools currently available to guide clinical diagnosis of Drug-Induced Liver Injury (DILI): Roussel-Uclaf Causality Assessment Method (RUCAM), Digestive-Disease-Week Japan 2004 scale (DD ... Full text Link to item Cite

Nonalcoholic fatty liver disease: does sex matter?

Journal Article Hepatobiliary Surg Nutr · April 2019 Full text Link to item Cite

The influence of drug properties and host factors on delayed onset of symptoms in drug-induced liver injury.

Journal Article Liver Int · February 2019 BACKGROUND & AIMS: Most patients with drug-induced liver injury (DILI) manifest clinical symptoms while on therapy, while some patients manifest days or weeks after drug cessation (delayed onset). This challenges DILI causality assessment and diagnosis. Fa ... Full text Link to item Cite

Reply.

Journal Article Clin Gastroenterol Hepatol · October 2018 Full text Open Access Link to item Cite

Correction to: Identifying Nonalcoholic Fatty Liver Disease Advanced Fibrosis in the Veterans Health Administration.

Journal Article Dig Dis Sci · October 2018 The original version of the article unfortunately contained errors in Table 3, Risk Factor column headings "Age > 50 (n = 115)," "Age > 50-64 (n = 154)," and "Age > 65 + (n = 60)." ... Full text Open Access Link to item Cite

Identifying Nonalcoholic Fatty Liver Disease Advanced Fibrosis in the Veterans Health Administration.

Journal Article Dig Dis Sci · September 2018 BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Severe NAFLD with advanced fibrosis results in substantial morbidity and mortality. Associated with metabolic syndrome, NAFLD is often initially clinica ... Full text Link to item Cite

Interplay of gender, age and drug properties on reporting frequency of drug-induced liver injury.

Journal Article Regul Toxicol Pharmacol · April 2018 We examined the effect of gender, age, and drug properties on liver events reporting frequency (RF) to assess patient- and drug-related risks for drug-induced liver injury (DILI). We performed a data-mining analysis of the WHO VigiBase™ to 1) identify drug ... Full text Link to item Cite

Associations of gender and a proxy of female menopausal status with histological features of drug-induced liver injury.

Journal Article Liver Int · November 2017 BACKGROUND & AIM: Gender and menopause may contribute to type and severity of drug-induced liver injury (DILI) by influencing host responses to injury. The aim of this study was to assess the associations of gender and female age 50 [a proxy of menopause] ... Full text Link to item Cite

Nonalcoholic Steatohepatitis.

Journal Article Annu Rev Med · January 14, 2017 Nonalcoholic steatohepatitis (NASH) has become a major cause of cirrhosis and liver-related deaths worldwide. NASH is strongly associated with obesity and the metabolic syndrome, conditions that cause lipid accumulation in hepatocytes (hepatic steatosis). ... Full text Link to item Cite

Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis.

Journal Article Clin Gastroenterol Hepatol · January 2017 BACKGROUND & AIMS: Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. METHODS: We collected data from 3 large U.S. studies of patien ... Full text Link to item Cite

Drug-Induced Liver Injury.

Journal Article Biomed Res Int · 2017 Full text Link to item Cite

Evaluation of multiple mechanism-based toxicity endpoints in primary cultured human hepatocytes for the identification of drugs with clinical hepatotoxicity: Results from 152 marketed drugs with known liver injury profiles.

Journal Article Chem Biol Interact · August 5, 2016 We report here the results of a collaborative research program to develop a robust and reliable in vitro system to allow an accurate definition of the drug-induced liver injury (DILI) potential of new drug entities during drug development. The in vitro hep ... Full text Link to item Cite

A longer duration of estrogen deficiency increases fibrosis risk among postmenopausal women with nonalcoholic fatty liver disease.

Journal Article Hepatology · July 2016 UNLABELLED: Postmenopausal women with nonalcoholic steatohepatitis are at an increased risk of hepatic fibrosis compared with premenopausal women. Whether duration of estrogen deficiency in postmenopausal state dictates an individual's fibrosis risk remain ... Full text Link to item Cite

Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration.

Journal Article World J Gastroenterol · May 21, 2016 AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement. METHODS: We performed a retrospective cohort study using a national repos ... Full text Open Access Link to item Cite

Comedications alter drug-induced liver injury reporting frequency: Data mining in the WHO VigiBase™.

Journal Article Regul Toxicol Pharmacol · August 2015 Polypharmacy is common, and may modify mechanisms of drug-induced liver injury. We examined the effect of these drug-drug interactions on liver safety reports of four drugs highly associated with hepatotoxicity. In the WHO VigiBase™, liver event reports we ... Full text Link to item Cite

Drug-induced liver injury: Interactions between drug properties and host factors.

Journal Article J Hepatol · August 2015 Idiosyncratic drug-induced liver injury (DILI) is a common cause for drug withdrawal from the market and although infrequent, DILI can result in serious clinical outcomes including acute liver failure and the need for liver transplantation. Eliminating the ... Full text Link to item Cite

Reply: To PMID 24849310.

Journal Article Hepatology · May 2015 Full text Link to item Cite

Reply: To PMID 24123276.

Journal Article Hepatology · March 2015 Full text Link to item Cite

Treatment response in the PIVENS trial is associated with decreased Hedgehog pathway activity.

Journal Article Hepatology · January 2015 UNLABELLED: Hedgehog (Hh) ligand production by ballooned hepatocytes drives nonalcoholic steatohepatitis (NASH) progression in mice. The NIDDK-sponsored PIVENS trial (NCT00063622) showed that vitamin E (VitE) improved NASH. We investigated whether VitE tre ... Full text Link to item Cite

Impact of gastrectomy on high-density lipoprotein cholesterol elevation in nonobese patients during a 10-year follow-up.

Journal Article J Atheroscler Thromb · 2015 AIM: The role of gastrectomy in glycemic control has been established in the current era of bariatric surgery for obesity. Gastrectomy in obese patients is associated with increased levels of high-density lipoprotein cholesterol (HDL-C). However, limited d ... Full text Link to item Cite

Repair-related activation of hedgehog signaling in stromal cells promotes intrahepatic hypothyroidism.

Journal Article Endocrinology · November 2014 Thyroid hormone (TH) is important for tissue repair because it regulates cellular differentiation. Intrahepatic TH activity is controlled by both serum TH levels and hepatic deiodinases. TH substrate (T4) is converted into active hormone (T3) by deiodinase ... Full text Link to item Cite

Age-related differences in reporting of drug-associated liver injury: data-mining of WHO Safety Report Database.

Journal Article Regul Toxicol Pharmacol · November 2014 BACKGROUND/AIMS: Age-differences in the frequency and manifestations of drug-induced liver injury are not fully characterized. Data-mining analyses were performed to assess the impact of age on liver event reporting frequency with different phenotypes and ... Full text Link to item Cite

No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial.

Journal Article Gastroenterology · August 2014 BACKGROUND & AIMS: n-3 polyunsaturated fatty acids reduce insulin resistance, lipogenesis, and inflammation, which are features of nonalcoholic steatohepatitis (NASH). Ethyl-eicosapentanoic acid (EPA-E) is a synthetic polyunsaturated fatty acid that reduce ... Full text Link to item Cite

Prevalence and natural history of histologically proven chronic liver disease in a longitudinal cohort of patients with type 1 diabetes.

Journal Article Hepatology · July 2014 UNLABELLED: Although a higher prevalence of raised liver enzymes and altered echotexture on ultrasound have been reported in patients with type 1 diabetes mellitus (T1DM), the histological spectrum and natural history of chronic liver disease (CLD) in T1DM ... Full text Link to item Cite

Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication.

Journal Article Clin Sci (Lond) · June 2014 OPN (osteopontin)) is a Hh (Hedgehog)-regulated cytokine that is up-regulated during chronic liver injury and directly promotes fibrosis. We have reported that Hh signalling enhances viral permissiveness and replication in HCV (hepatitis C virus)-infected ... Full text Link to item Cite

Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis.

Conference Hepatology · April 2014 UNLABELLED: Estrogens inhibit stellate cell activation and fibrogenesis. Thus, gender and reproductive states may influence the degree of fibrosis in patients with nonalcoholic steatohepatitis (NASH). To investigate the association between gender, menopaus ... Full text Link to item Cite

Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease.

Journal Article Hepatology · February 2014 UNLABELLED: Clinicians rely upon the severity of liver fibrosis to segregate patients with well-compensated nonalcoholic fatty liver disease (NAFLD) into subpopulations at high- versus low-risk for eventual liver-related morbidity and mortality. We compare ... Full text Link to item Cite

Mining hidden knowledge for drug safety assessment: topic modeling of LiverTox as a case study.

Journal Article BMC Bioinformatics · 2014 BACKGROUND: Given the significant impact on public health and drug development, drug safety has been a focal point and research emphasis across multiple disciplines in addition to scientific investigation, including consumer advocates, drug developers and ... Full text Link to item Cite

NASH in special populations

Journal Article Gastroenterology and Hepatology · January 1, 2014 Cite

Relationship between methylome and transcriptome in patients with nonalcoholic fatty liver disease.

Journal Article Gastroenterology · November 2013 BACKGROUND & AIMS: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting noninvasive diagnosis and treat ... Full text Link to item Cite

Complete Esophageal Obstruction after Endoscopic Variceal Ligation

Conference American Journal of Gastroenterology · October 2013 Full text Cite

Associations of depression, anxiety and antidepressants with histological severity of nonalcoholic fatty liver disease.

Journal Article Liver Int · August 2013 BACKGROUND: Depression and anxiety are common in patients with nonalcoholic fatty liver disease (NAFLD). However, their associations with histological severity of NAFLD are unknown. AIM: This study examined the association(s) of depression, anxiety and ant ... Full text Link to item Cite

Hedgehog pathway and pediatric nonalcoholic fatty liver disease.

Journal Article Hepatology · May 2013 UNLABELLED: It is unclear why the histology of pediatric and adult nonalcoholic fatty liver disease (NAFLD) sometimes differs. In adults, severity of portal inflammation and fibrosis correlate with Hedgehog pathway activity. Hedgehog (Hh) signaling regulat ... Full text Link to item Cite

Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis.

Journal Article FASEB J · April 2013 Choline metabolism is important for very low-density lipoprotein secretion, making this nutritional pathway an important contributor to hepatic lipid balance. The purpose of this study was to assess whether the cumulative effects of multiple single nucleot ... Full text Link to item Cite

Characterizing phenotypes and outcomes of drug-associated liver injury using electronic medical record data.

Journal Article Pharmacoepidemiol Drug Saf · February 2013 PURPOSE: To evaluate the incidence, phenotypes, and outcomes of drug-associated liver injury identified in electronic medical record (EMR) data using standardized criteria for drug-induced liver injury (DILI). METHODS: This retrospective cohort study used ... Full text Link to item Cite

Prevalence and indicators of portal hypertension in patients with nonalcoholic fatty liver disease.

Journal Article Clin Gastroenterol Hepatol · September 2012 BACKGROUND & AIMS: Little is known about the prevalence and severity of portal hypertension in patients with nonalcoholic fatty liver disease (NAFLD). We investigated the prevalence and noninvasive predictors of portal hypertension in patients with NAFLD. ... Full text Link to item Cite

A pre-marketing ALT signal predicts post-marketing liver safety.

Journal Article Regul Toxicol Pharmacol · August 2012 Drug induced liver injury during drug development is evidenced by a higher incidence of serum alanine aminotransferase (ALT) elevations in treated versus placebo populations and termed an "ALT signal". We sought to quantify whether an ALT signal in pre-mar ... Full text Link to item Cite

Association between puberty and features of nonalcoholic fatty liver disease.

Journal Article Clin Gastroenterol Hepatol · July 2012 BACKGROUND & AIMS: Physiological changes that occur during puberty might affect pathologic features of nonalcoholic fatty liver disease (NAFLD). We investigated associations between pubertal development and clinical and histopathologic features of NAFLD. M ... Full text Link to item Cite

Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease.

Journal Article Hum Pathol · June 2012 Nonalcoholic fatty liver disease is a global health dilemma. The gold standard for diagnosis is liver biopsy. Ballooned hepatocytes are histologic manifestations of hepatocellular injury and are characteristic of steatohepatitis, the more severe form of no ... Full text Link to item Cite

Hedgehog pathway activation parallels histologic severity of injury and fibrosis in human nonalcoholic fatty liver disease.

Journal Article Hepatology · June 2012 UNLABELLED: The Hedgehog (HH)-signaling pathway mediates several processes that are deregulated in patients with metabolic syndrome (e.g., fat mass regulation, vascular/endothelial remodeling, liver injury and repair, and carcinogenesis). The severity of n ... Full text Link to item Cite

Epigenetic Regulation of Gene Expression in NAFLD

Conference GASTROENTEROLOGY · May 1, 2012 Link to item Cite

The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury.

Journal Article Hepatology · September 2, 2011 UNLABELLED: Distinguishing drug-induced liver injury (DILI) from idiopathic autoimmune hepatitis (AIH) can be challenging. We performed a standardized histologic evaluation to explore potential hallmarks to differentiate AIH versus DILI. Biopsies from pati ... Full text Link to item Cite

Increased production of sonic hedgehog by ballooned hepatocytes.

Journal Article J Pathol · July 2011 Ballooned hepatocytes distinguish non-alcoholic steatohepatitis (NASH) from steatosis. Such cells contain dilated endoplasmic reticulum and ubiquitin aggregates, characteristics of endoplasmic reticulum stress. Hepatocyte ballooning increases the risk for ... Full text Link to item Cite

Drug induced hepatotoxicity: data from the Serbian pharmacovigilance database.

Journal Article Pharmacoepidemiol Drug Saf · April 2011 PURPOSE: The main aim of this study was to determine the most frequently reported drugs to the Serbian Pharmacovigilance Database (SPD) with suspected induced hepatotoxicity. Additionally, reasons for the low reporting rate of adverse drug reactions (ADRs) ... Full text Link to item Cite

Regional anthropometric measures and hepatic fibrosis in patients with nonalcoholic Fatty liver disease.

Journal Article Clin Gastroenterol Hepatol · December 2010 BACKGROUND & AIMS: In overnourished individuals, impaired peripheral fat storage (ie, reduced fat mass in extremities) can increase delivery of surplus calories to the organs other than peripheral adipose tissues, including the liver (ie, lipid overload), ... Full text Link to item Cite

Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease.

Journal Article Hepatology · June 2010 UNLABELLED: The rising incidence of obesity and diabetes coincides with a marked increase in fructose consumption. Fructose consumption is higher in individuals with nonalcoholic fatty liver disease (NAFLD) than in age-matched and body mass index (BMI)-mat ... Full text Link to item Cite

Does pain predict interference with daily functioning and weight loss in an obese residential treatment-seeking population?

Journal Article Int J Behav Med · June 2010 BACKGROUND: Pain may interfere with daily functioning in obese persons and also with outcomes during weight loss. We examined the relationship between pain and (1) interference with daily functioning (DFi) and (2) outcomes in an obese treatment-seeking pop ... Full text Link to item Cite

Drugs associated with hepatotoxicity and their reporting frequency of liver adverse events in VigiBase: unified list based on international collaborative work.

Journal Article Drug Saf · June 1, 2010 BACKGROUND: Challenges exist in the clinical diagnosis of drug-induced liver injury (DILI) and in obtaining information on hepatotoxicity in humans. OBJECTIVE: (i) To develop a unified list that combines drugs incriminated in well vetted or adjudicated DIL ... Full text Link to item Cite

Serum aminotransferase changes with significant weight loss: sex and age effects.

Journal Article Metabolism · February 2010 In obese subjects, the liver may be differentially affected by significant weight loss depending on as yet unknown factors. We explored clinical factors associated with serum alanine aminotransferase (ALT) changes during significant weight loss in a reside ... Full text Link to item Cite

Sleep disturbance and pain in an obese residential treatment-seeking population.

Journal Article Clin J Pain · September 2009 BACKGROUND: The relationships between body mass index (BMI) and sleep disturbance, sleep disturbance and pain, and obesity and pain are documented; however, there is a paucity of research exploring how sleep relates to pain in obese populations. METHOD: Th ... Full text Link to item Cite

Co-medications that modulate liver injury and repair influence clinical outcome of acetaminophen-associated liver injury.

Journal Article Clin Gastroenterol Hepatol · August 2009 BACKGROUND & AIMS: Acetaminophen-induced liver injury is the most common cause of acute liver failure in the United States; it occurs inadvertently in approximately half of all cases. Concomitant use of other medications might impact susceptibility to acet ... Full text Link to item Cite

Nonalcoholic fatty liver disease in women.

Journal Article Womens Health (Lond) · March 2009 Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed countries and is increasing in prevalence with the rise of diabetes and obesity. In addition to obesity and age, gender may also influence the prevalence an ... Full text Link to item Cite

Surveillance for hepatocellular carcinoma in patients with primary biliary cirrhosis.

Journal Article Hepatology · October 2008 UNLABELLED: Hepatocellular carcinoma (HCC) occurs with increased frequency in patients with primary biliary cirrhosis (PBC). Effectiveness of surveillance recommendations for HCC is controversial, and data are lacking in patients with PBC. In this study, w ... Full text Link to item Cite

SLEEP DISTURBANCE AND PAIN IN AN OBESE RESIDENTIAL TREATMENT SEEKING POPULATION

Conference ANNALS OF BEHAVIORAL MEDICINE · December 1, 2007 Link to item Cite

Light to moderate alcohol consumption is associated with lower frequency of hypertransaminasemia.

Journal Article Am J Gastroenterol · September 2007 OBJECTIVES: The effect of light to moderate alcohol consumption on the liver is controversial. To determine the association between light to moderate alcohol consumption and frequency of hypertransaminasemia, a cross-sectional and a subsequent longitudinal ... Full text Link to item Cite

Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation.

Journal Article Lab Invest · May 2007 In bile duct-ligated (BDL) rodents, as in humans with chronic cholangiopathies, biliary obstruction triggers proliferation of bile ductular cells that are surrounded by fibrosis produced by adjacent myofibroblastic cells in the hepatic mesenchyme. The prox ... Full text Link to item Cite

Clinical predictors for hepatocellular carcinoma in patients with primary biliary cirrhosis.

Journal Article Clin Gastroenterol Hepatol · February 2007 BACKGROUND & AIMS: Although hepatocellular carcinoma (HCC) occurs with increased frequency in patients with primary biliary cirrhosis (PBC), the exact frequency is relatively low. Optimal selection of PBC patients for HCC screening needs to be determined f ... Full text Link to item Cite

Values and limitations of serum aminotransferases in clinical trials of nonalcoholic steatohepatitis.

Journal Article Liver Int · December 2006 BACKGROUND/AIMS: Choosing endpoints in nonalcoholic steatohepatitis (NASH) trials is challenging because of the lack of validated surrogates and the trade-off between accuracy and invasiveness. In this study, we assessed diagnostic accuracy of serum aminot ... Full text Link to item Cite

Serum insulin levels and the prevalence of adenomatous and hyperplastic polyps in the proximal colon.

Journal Article Clin Gastroenterol Hepatol · October 2006 BACKGROUND & AIMS: Obesity and diabetes mellitus are associated with an increased incidence of proximal colon cancer. Colonic adenoma that has been reported to be associated with elevated serum insulin levels and subsets of hyperplastic polyps might serve ... Full text Link to item Cite

Interleukin-15 increases hepatic regenerative activity.

Journal Article J Hepatol · September 2006 BACKGROUND/AIMS: Interleukin-15 (IL-15) is expressed in many organs. It generally inhibits apoptosis and increases cellular proliferation and differentiation. However, IL-15's roles in liver are unknown. We aimed to determine if IL-15 influences hepatic in ... Full text Link to item Cite

Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease.

Journal Article J Hepatol · December 2005 BACKGROUND/AIMS: The effects of lifestyle modifications in nonalcoholic fatty liver disease (NAFLD) are incompletely defined. We aimed at determining the association of changes in body weight and lifestyle with changes in serum ALT levels. METHODS: We anal ... Full text Link to item Cite

Hyaluronic acid, an accurate serum marker for severe hepatic fibrosis in patients with non-alcoholic fatty liver disease.

Journal Article Liver Int · August 2005 AIM: To determine whether serum hyaluronic acid reliably predicts the severity of hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: We studied 79 patients with histologically confirmed NAFLD. Hyaluronic acid was measured ... Full text Link to item Cite

Risk of colorectal neoplasm in patients with acromegaly and its relationship with serum growth hormone levels.

Journal Article Am J Gastroenterol · May 2005 OBJECTIVES: Acromegalics have been reported to be at an increased risk of colorectal neoplasm. However, the magnitude of the risk is still controversial and the mechanism has not been fully investigated. In this study, we attempted to determine the magnitu ... Full text Link to item Cite

Diagnostic model of esophageal varices in alcoholic liver disease.

Journal Article Eur J Gastroenterol Hepatol · March 2005 Esophageal varices may cause life-threatening bleeding with attendant high hospital cost. Since effective preventive modalities for variceal hemorrhage have been established, early detection of esophageal varices is critical for prevention of bleeding. Cur ... Full text Link to item Cite

Chronological development of elevated aminotransferases in a nonalcoholic population.

Journal Article Hepatology · January 2005 The incidence and risk factors of nonalcoholic fatty liver disease (NAFLD) have never been prospectively determined. To determine the frequency and risk factors of NAFLD and chronological ordering between NAFLD, weight gain, and features of insulin resista ... Full text Link to item Cite

Oral tolerance and pyruvate dehydrogenase in patients with primary biliary cirrhosis.

Journal Article Dev Immunol · June 2002 Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the immunological destruction of intralobular bile ducts and serum anti-mitochondrial antibodies (AMA). Based upon previous work of oral tolerance and autoimmunity, we ... Full text Link to item Cite

Effect of bilirubin UDP glucuronosyltransferase 1 gene TATA box genotypes on serum bilirubin concentrations in chronic liver injuries.

Journal Article Hepatology · September 2000 TATA box abnormality in the promoter region of the bilirubin UDP glucuronosyltransferase 1 gene has been reported to cause Gilbert's syndrome in white subjects. It has also been reported that the majority of Japanese patients with Gilbert's syndrome are he ... Full text Link to item Cite

[Cowden disease].

Journal Article Nihon Rinsho · July 2000 Cowden disease is an autosomal dominant disorder associated with an increased risk of developing benign and malignant tumors in many organ systems including the breast, thyroid, skin, central nervous system and gastrointestinal tract. Recently, germline mu ... Link to item Cite

Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.

Journal Article Hum Mutat · 2000 The gene ATP7B responsible for Wilson's disease (WD) produces a protein which is predicted to be a copper-binding P-type ATPase, homologous to the Menkes disease gene (ATP7A). Various mutations of ATP7B have been identified. This study aimed to detect dise ... Full text Link to item Cite

Effect of bacterial or porcine lipase with low- or high-fat diets on nutrient absorption in pancreatic-insufficient dogs.

Journal Article Gastroenterology · February 1999 BACKGROUND & AIMS: Treatment of human exocrine pancreatic insufficiency is suboptimal. This study assessed the effects of bacterial lipase, porcine lipase, and diets on carbohydrate, fat, and protein absorption in pancreatic-insufficient dogs. METHODS: Dog ... Full text Link to item Cite

Bacterial lipase and high-fat diets in canine exocrine pancreatic insufficiency: a new therapy of steatorrhea?

Journal Article Gastroenterology · June 1997 BACKGROUND & AIMS: Nutrients and properties of lipases affect survival of lipolytic activity during aboral gastrointestinal transit. Whether different doses and formulations of bacterial lipase and diets affect steatorrhea was tested in pancreatic-insuffic ... Full text Link to item Cite

[Cowden's disease].

Journal Article Nihon Rinsho · December 1991 Link to item Cite

Nonalcoholic Fatty Liver Disease

Journal Article Karnataka Medical Journal Cite